Association of Isocitrate Dehydrogenase (IDH) Status With Edema to Tumor Ratio and Its Correlation With Immune Infiltration in Glioblastoma.

Daniel Dubinski,Joshua D Bernstock,Maximilian Rauch,Peter Baumgarten,Volker Seifert,Bedjan Behmanesh,Thomas M Freiman,Lionel D C Ngassam,Patrick N Harter,Christian Senft,Sae-Yeon Won,Florian Gessler

doi:10.3389/fimmu.2021.627650

Abstract

PurposeThe extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.MethodsA volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.ResultsThe edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups.ConclusionIn our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.

Highlights

Glioblastoma (GBM) patients frequently present with peritumoral edema as diagnosed with preoperative imaging, such as T2 or FLAIR MRI scan
Several studies have identified the synthetic corticosteroid dexamethasone (DEX) as unbeneficial in terms of survival for edema treatment in GBM, it is still routinely used in clinics for peritumoral edema treatment in GBM [3, 4]
Patient characteristics that were extracted from the medical chart including the preoperative Karnofsky performance scale (KPS), date of surgery, date of death or date of last contact, date of tumor progression that was defined as the date of cranial MRI with progressive disease according to the RANO [8] criteria and/ or the determination of the local interdisciplinary neurooncological tumor board

Summary

Introduction

Glioblastoma (GBM) patients frequently present with peritumoral edema as diagnosed with preoperative imaging, such as T2 or FLAIR MRI scan. Peritumoral edema in turn often causes severe neurological impairment and remains a challenging factor throughout treatment [1]. The peritumoral edema in GBM is considered to be vasogenic and caused by increased vascular permeability as hypoxia induced capillary formations lack functional tight junctions, contain fenestration and irregular basal membrane endothelia [2]. The hypoxic core of the GBM, often containing necrosis, results in VEGF secretion which in turn is a crucial mediator of peritumoral edema and disrupted tissue hemostasis. Several studies have identified the synthetic corticosteroid dexamethasone (DEX) as unbeneficial in terms of survival for edema treatment in GBM, it is still routinely used in clinics for peritumoral edema treatment in GBM [3, 4]

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Results

Conclusion